Dorsal root ganglion (DRG) and ventral spinal cord (VSC) neurons were grown in a compartmented cell culture chamber such that their axonal protein composition could be compared after metabolic labelling and SDS-polyacrylamide gel electrophoresis. While there is a high degree of similarity between the two cell types with respect to their axonal protein, each type has several proteins which are markedly reduced or absent in the other. We have used this system to examine changes in the pattern of newly synthesized axonal proteins that coincide with early events in synapse formation between DRG and VSC neurons. Among the approximately 300 DRG axonal proteins visualized, four changed their relative abundance markedly. One protein, with a molecular weight of about 65K, which was among the most abundant proteins under control conditions, diminished drastically during co-culture with VSC cells. Another minor protein with molecular weight of about 50K was clearly reduced. Concurrently, two proteins, both with a molecular weight of approximately 60K were found to be synthesized much more abundantly.